Subcardiac threshold vagal nerve stimulation

ABSTRACT

In one embodiment, an implantable stimulation apparatus includes a vagal nerve stimulator configured to generate electrical pulses below a cardiac threshold of a heart, and an electrode coupled to the vagal nerve stimulator which is configured to transmit the electrical pulses below the cardiac threshold, to a vagal nerve so as to inhibit injury resulting from an ischemia and/or reduce injury resulting from an ischemia. In another embodiment, an implantable stimulation apparatus includes a vagal nerve stimulator configured to generate electrical pulses below a cardiac threshold, and includes an electrode, which is coupled to the vagal nerve stimulator and configured transmit electrical pulses to a vagal nerve so as to reduce a defibrillation threshold of the heart.

PRIORITY CLAIM

This application is a Continuation Application of and claims priorityand other benefits from U.S. patent application Ser. No. 11/330,885(Attorney Docket No. A05P3025-US1), filed Jan. 11, 2006, entitled“SUBCARDIAC THRESHOLD VAGAL NERVE STIMULATION,” incorporated herein byreference in its entirety.

CROSS-REFERENCES TO RELATED APPLICATIONS

The subject matter of the present application is related to co-pendingU.S. patent application Ser. No. 11/330,884 (Attorney Docket No.A05P3025-US2), filed Jan. 11, 2006, entitled “Subcardiac Threshold VagalNerve Stimulation” which is herein incorporated by reference in itsentirety.

BACKGROUND

Implantable devices for stimulating vagal nerves may be used to treatvarious medical conditions of a patient. Typically, an implantabledevice generates electrical pulses and delivers the electrical pulses toa vagal nerve of the patient to treat a particular medical condition. Inmany cases, this treatment can have the undesired effects of beinguncomfortable to the patient, and causing a reduction in the patient'sheart beat rate.

One approach to counter the slowing of the patient's heart beat rate isto stimulate the heart with pacing pulses. Thus, the vagal nerve isstimulated to treat the medical condition, and the heart is stimulatedto maintain a normal heart beat rate during treatment. Stimulation ofthe heart during treatment, however, consumes power in the implantabledevice, which reduces the maximum possible duration for the treatment.Consequently, the medical condition may not be adequately treated withthis approach.

In light of the above, there exists a need for stimulating a vagal nerveto treat a medical condition without pacing a patient's heart. Therefurther exists a need for an implantable device that stimulates a vagalnerve for a prolonged period to treat a medical condition.

SUMMARY

In one embodiment, an implantable stimulation apparatus is providedwhich includes a vagal nerve stimulator configured to generateelectrical pulses below a cardiac threshold of a heart. An electrode iscoupled to the vagal nerve stimulator and is configured to transmit theelectrical pulses, which are below the cardiac threshold, to a vagalnerve so as to inhibit injury resulting from an ischemia and/or reduceinjury resulting from an ischemia.

In some implementations, a method is provided which includes generatingelectrical pulses below a cardiac threshold and treating an ischemia bytransmitting the electrical pulses below the cardiac threshold to avagal nerve.

In another embodiment, an implantable stimulation apparatus is providedwhich includes a vagal nerve stimulator configured to generateelectrical pulses below a cardiac threshold. The implantable stimulationapparatus includes an electrode, which is coupled to the vagal nervestimulator and configured transmit electrical pulses to a vagal nerve soas to reduce a defibrillation threshold of the heart.

In some implementations, a method is provided which includes generatingelectrical pulses below a cardiac threshold of a heart and transmittingthe electrical pulses to a vagal nerve for reducing a defibrillationthreshold of the heart.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a simplified diagram of an embodiment of an implantablesubcardiac threshold vagal nerve stimulation apparatus.

FIG. 2 is a simplified diagram of an embodiment of an additionalimplantable subcardiac threshold vagal nerve stimulation apparatus.

FIG. 3 is a simplified diagram of an embodiment of an implantablesubcardiac threshold vagal nerve stimulation apparatus.

FIG. 4 is a functional block diagram of a possible embodiment of animplantable subcardiac threshold vagal nerve stimulation apparatus.

FIG. 5 is a functional block diagram of an exemplary heart stimulator.

FIG. 6 is a diagram of an exemplary lead portion.

FIG. 7 is a diagram of an exemplary lead portion.

FIG. 8 is a diagram of an exemplary lead portion.

FIG. 9 is a diagram of an exemplary lead portion.

FIG. 10 is an approximate anatomical diagram of the heart and variousstructures including the right vagal nerve.

FIG. 11 is a diagram of an exemplary arrangement whereby an exemplarylead portion is positioned in the SVC for activation of a branch of theright vagal nerve.

FIG. 12 is a diagram of an exemplary lead portion.

FIG. 13 is a diagram of an exemplary lead portion.

FIG. 14 is a diagram of an exemplary lead portion.

FIG. 15 is a diagram of an exemplary lead portion.

FIG. 16 is a diagram of an exemplary lead portion.

FIG. 17 is a flowchart for a method of treating an ischemia.

FIG. 18 is a flowchart for a method of treating an ischemia.

FIG. 19 is a flowchart for a method of reducing a defibrillationthreshold.

DETAILED DESCRIPTION

The following description includes the best mode presently contemplatedfor practicing the described implementations. This description is not tobe taken in a limiting sense, but rather is made merely for the purposeof describing the general principles of the implementations. The scopeof the described implementations should be ascertained with reference tothe issued claims. In the description that follows, like numerals orreference designators will be used to reference like parts or elementsthroughout.

There are several potential benefits from subcardiac threshold vagalstimulation. Subcardiac threshold vagal stimulation may be used toinhibit release of pro-inflammatory endotoxins. As such, it is possibleto treate ischemia with subcardiac threshold vagal stimulation toreduce, or inhibiting ischemia insult, without the above discusseddrawbacks. Furthermore, subcardiac threshold vagal stimulation may beused to reduce the diffibrillation threshold of a patient without theabove discussed drawbacks.

FIGS. 1-3 show examples of possible embodiments capable of subcardiacvagal threshold nerve stimulation apparatus in accordance with thepresent invention. In the embodiment of FIG. 1, an implantablesubcardiac threshold vagal nerve stimulation apparatus 1 is coupled incommunication via a lead 48 to stimulation electrodes 34 and 38 suitablefor subcardiac threshold stimulation of vagal nerve 30 stimulation. Invarious embodiments, the implantable subcardiac threshold vagal nervestimulation apparatus 1 includes a means of delivering this energy toanywhere between the cervical and the preganglionic cardiac fibers toprovide subcardiac threshold vagal input to the autonomic ganglions,which activates the nicotinic receptors on the post-ganglionic fibers.The implantable subcardiac threshold vagal nerve stimulation apparatus30 includes a vagal nerve stimulator (shown in FIG. 3), such as a pulsegenerator that generates low level pulse trains, to stimulate the vagus.In the embodiment of FIG. 1, the stimulation electrodes 34 and 38 arepositioned adjacent the vagal nerve 32 with a helical or a cork screwshaped portion 46 of the lead 48, which may be partially or completelywound around the vagal nerve 32. The stimulation electrodes 34 and 38(or additional electrodes) may be in contact with the vagas nerve tostimulate it directly, or it may be near the vagas nerve and stimulateit indirectly.

In the embodiment shown in FIG. 1, the implatable subcardiac thresholdvagal nerve stimulation apparatus 30 includes optional heart activitysensors 50 and 54 capable of sensing for heart activity. As such, theheart sensors 50 and 54 may be electrodes embedded in the case 42 usedto capture electrocardiogram signals. In some embodiments, the sensors50 and 54 may be outside the case 42 and connected by leads (not shown),or wirelessly. The leads may be placed subcutaneously, epicardially, orendocardially. In other embodiments (not shown), the sensors 50 and 54may be omitted. For example, the sensors may be omitted in someembodiments used to treat ischemia. If used prior to an ischemia, toinhibit injury from the ischemia, the sensing of electrocardiograms maynot be necessary to apply therapy.

On the other hand, in some embodiments the sensors such as 50 and 54 maybe exploited. For example, in some embodiments adapted to lower thedefibrillation threshold during ventricular fibrillation, sensors suchas 50 and 54 can provide information for input to an algorithm, whichmay used to detect the onset of the ventricular fibrillation. Ifventricular fibrillation is detected, subcardiac threshold vagal nervestimulation is activated to reduce the defibrillation threshold, priorto and/or during defibrillation. As such, in yet other embodiments, oneor more of the sensors 50 and 54 may be part of one or more endocardialleads, such as shown in FIG. 3. Furthermore, the ability to monitorcardiac activations can provide a feedback mechanism to ensure thestimulation strengths are below the cardiac threshold.

FIG. 2 shows another possible embodiment of an implantable subcardiacthreshold vagal nerve stimulation apparatus 60. In the embodiment ofFIG. 2, the implantable subcardiac threshold vagal nerve stimulationapparatus 60 includes flexible flaps 68 a and 68 b that may be wrappedaround the vagal nerve 62, as illustrated by the arrows, to hold thestimulation electrodes 72 and 74 adjacent the vagal nerve 62. Otheranchoring mechanisms to secure placement of the electrodes and/or theimplantable subcardiac threshold vagal nerve stimulation apparatus 60 bythe nerve are possible. The embodiment of FIG. 2 is shown with heartactivity sensors 64 and 78 embedded in the case 76.

In various embodiments, the implantable subcardiac threshold vagal nervestimulation apparatus 60 is capable of sensing cardiac electricalactivations, possibly from two, or more, active electrodes on the case42 or 76, one or more electrodes placed sub-cutaneously with the case asthe active electrode, or one or more electrodes placedendocardially/epicardially, with the case 42 or 76 as an activeelectrode.

Turning to FIG. 3, in one possible embodiment, a subcardiac thresholdvagal nerve stimulation apparatus may include, or be part of, aimplantable cardiac rhythm management device, or vice-versa. FIG. 3shows an example implantable stimulation apparatus 100 which includes asubcardiac threshold vagal nerve stimulator (shown in FIG. 4). Theimplantable stimulation apparatus 100 is coupled via a lead 110 to threeelectrodes 144, 144′, 144″ suitable for stimulation of autonomic nervessuch as non-myocardial tissue, vagal nerves, or other nerves. Forexample, the lead 110 may be positioned in and/or near a patient's heart102 or near an autonomic nerve within a patient's body and remote fromthe heart 102. The lead 110 optionally includes an exemplary leadportion, as described in further detail below. Although three electrodes144, 144′, and 144″ are shown in FIG. 3, the implantable stimulationapparatus 100 may be in electrical communication with the patient'svagal nerves via fewer or more electrodes.

In this embodiment, the implantable stimulation apparatus 100 is showncoupled in electrical communication with the heart 102 via three leads104, 106, 108, suitable for delivering multi-chamber stimulation andshock therapy. The leads 104, 106, 108 are optionally configurable fordelivery of stimulation pulses suitable for stimulation of autonomicnerves, non-myocardial tissue, other nerves, etc. The right atrial lead104, as the name implies, is positioned in and/or passes through apatient's right atrium. The right atrial lead 104 optionally sensesatrial cardiac signals and/or provide right atrial chamber stimulationtherapy. As shown in FIG. 3, the implantable stimulation apparatus 100is coupled to an implantable right atrial lead 104 having, for example,an atrial tip electrode 120, which typically is implanted in thepatient's right atrial appendage. The lead 104, as shown in FIG. 3, alsoincludes an atrial ring electrode 121. Of course, the lead 104 may haveother electrodes as well. For example, the right atrial lead optionallyincludes a distal bifurcation having electrodes suitable for stimulationof autonomic nerves, non-myocardial tissue, other nerves, etc. The rightatrial lead 104 optionally includes an exemplary lead portion, asdescribed in further detail below.

To sense atrial cardiac signals, ventricular cardiac signals and/or toprovide chamber pacing therapy, particularly on the left side of apatient's heart, the implantable stimulation apparatus 100 is coupled toa coronary sinus lead 106 designed for placement in the coronary sinusand/or tributary veins of the coronary sinus. Thus, the coronary sinuslead 106 is optionally suitable for positioning at least one distalelectrode adjacent to the left ventricle and/or additional electrode(s)adjacent to the left atrium. In a normal heart, tributary veins of thecoronary sinus include, but may not be limited to, the great cardiacvein, the left marginal vein, the left posterior ventricular vein, themiddle cardiac vein, and the small cardiac vein.

Accordingly, an exemplary coronary sinus lead 106 is optionally designedto receive atrial and ventricular cardiac signals and to deliver leftventricular pacing therapy using, for example, at least a leftventricular tip electrode 122, left atrial pacing therapy using at leasta left atrial ring electrode 124, and shocking therapy using at least aleft atrial coil electrode 126. For a complete description of a coronarysinus lead, the reader is directed to U.S. patent application Ser. No.09/457,277, filed Dec. 08, 1999, entitled “A Self-Anchoring, SteerableCoronary Sinus Lead” (Pianca et al.); and U.S. Pat. No. 5,466,254,“Coronary Sinus Lead with Atrial Sensing Capability” (Helland), whichare incorporated herein by reference. The coronary sinus lead 106further optionally includes electrodes for stimulation of autonomicnerves. Such a lead may include pacing and autonomic nerve stimulationfunctionality and may further include bifurcations or legs. For example,an exemplary coronary sinus lead includes pacing electrodes capable ofdelivering pacing pulses to a patient's left ventricle and at least oneelectrode capable of stimulating an autonomic nerve. An exemplarycoronary sinus lead (or left ventricular lead or left atrial lead) mayalso include at least one electrode capable of stimulating an autonomicnerve, non-myocardial tissue, other nerves, etc., wherein such anelectrode may be positioned on the lead or a bifurcation or leg of thelead. A coronary sinus lead 106 optionally includes an exemplary leadportion, as described in further detail below.

The implantable stimulation apparatus 100 is also shown in electricalcommunication with the patient's heart 102 by way of an implantableright ventricular lead 108 having, in this exemplary implementation, aright ventricular tip electrode 128, a right ventricular ring electrode130, a right ventricular (RV) coil electrode 132, and a superior venacava (SVC) coil electrode 134. Typically, the right ventricular lead 108is transvenously inserted into the heart 102 to place the rightventricular tip electrode 128 in the right ventricular apex so that theRV coil electrode 132 will be positioned in the right ventricle and theSVC coil electrode 134 will be positioned in the superior vena cava.Accordingly, the right ventricular lead 108 is capable of sensing orreceiving cardiac signals, and delivering stimulation in the form ofpacing and shock therapy to the right ventricle. An exemplary rightventricular lead may also include at least one electrode capable ofstimulating an autonomic nerve, non-myocardial tissue, other nerves,etc., wherein such an electrode may be positioned on the lead or abifurcation or leg of the lead. The right ventricular lead 108optionally includes an exemplary lead portion, as described in furtherdetail below.

FIG. 4 shows an exemplary, simplified block diagram depicting variouscomponents of the implantable stimulation apparatus 100. The implantablestimulation apparatus 100 includes a housing 200 which may beprogrammably selected to act as the return electrode in combination withone or more of the electrodes 144, 144′, or 144″ for electricalstimulation of an autonomic nerve, such as a vagal nerve, or for sensingof cardiac activity occurring in the heart 102 (FIG. 3). The implantablestimulation apparatus 100 includes a vagal nerve stimulator 215 coupledin communication with both a control circuit 205 and the lead 110 (FIG.3). Optionally, the implantable stimulation apparatus 100 includes aheart stimulator 225 coupled in communication with the control circuit205, the right atrial lead 104 (FIG. 3), the coronary sinus lead 106(FIG. 3), and the right ventricular lead 108 (FIG. 3).

The vagal nerve stimulator 215 generates electrical pulses below acardiac threshold of the heart 102 (FIG. 3) for treating an ischemia ofthe heart 102, or for reducing a defibrillation threshold of the heart102. The cardiac threshold is a threshold for energy delivered to theheart 102 above which there is a slowing of the heart rate or theconduction velocity. In operation, the vagal nerve stimulator 215generates the electrical pulses below the cardiac threshold (i.e.,subcardiac threshold electrical pulses) such that the beat rate of theheart 102 is not affected. In one embodiment, the energy of theelectrical pulses is just below the subcardiac threshold to providemaximum stimulation to a vagal nerve. The frequency of the electricalpulses may be in a range of 10 to 100 Hz. For example, the frequency ofthe electrical pulses may be 20 Hz. The voltage amplitude of theelectrical pulses may be in a range of 0.5 to 20 V. For example, thevoltage amplitude of the electrical pulses may be below 5 V. The pulsewidth of the electrical pulses may be in a range of 0.1 to 5 msec. Forexample, the pulse width of the electrical pulses may be 2 msec.

In one embodiment, the energy of the electrical pulses is substantiallybelow the subcardiac threshold to increase the battery life of the vagalnerve stimulator 215 and thus increase the maximum possible duration oftreatment or therapy. Although the function of the vagal nervestimulator 215 described above is to treat an ischemia, or to reduce adefibrillation threshold of the heart 102, in other embodiments thevagal nerve stimulator 215 may function to treat heart failure, reducean inflammatory response during a medical procedure, stimulate therelease of insulin for treating diabetes, suppress insulin resistancefor treating diabetes, or treat an infarction of the heart 102.

The vagal nerve stimulator 215 may also sense cardiac activity occurringin the heart 102 (FIG. 3). Such cardiac activity includes P-waves orR-waves occurring in the heart 102, as well as the beat rate of theheart 102. For example, the vagal nerve stimulator 215 may determine thebeat rate of the heart 102 based on the period between successiveP-waves, the period between successive R-waves, or the period between aP-wave and a successive R-wave. The vagal nerve stimulator 215 may sensethe cardiac activity via the leads 104, 106, 108, or 110 (FIG. 3), orany combination thereof. In various embodiments, the vagal nervestimulator 215 may also sense the cardiac activity via the case 200 incombination with one or more of the leads 104, 106, 108, or 110.

The electrical pulses generated by the vagal nerve stimulator 215 may becontinuous or periodic. An advantage of periodic pulses is thatadaptation of the vagal nerve to the electrical pulses is inhibited. Forexample, the electrical pulses may be generated for a period of 45seconds every 60 seconds. Alternatively, the electrical pulses may begenerated in response to a trigger event. An example of a trigger eventis cardiac activity, such as a P-wave or an R-wave, occurring in theheart 102. The electrical pulses may be generated for a period of timesubsequent to the trigger event for stimulating the vagal nerve.

The control circuit 205 controls operation of the vagal nerve stimulator215 via a control signal 210. The control circuit 205 may includedigital logic circuits, analog logic circuits, or computer software. Forexample, the control circuit may be a computing processor, such as amicroprocessor or a microcontroller. The control circuit 205 may controlthe energy of the electrical pulses generated by the vagal nervestimulator 215. For example, the control circuit 205 may control theenergy of the electrical pulses based on cardiac activity occurring inthe heart 102 (FIG. 3) such that the electrical pulses do not exceed thesubcardiac threshold of the heart 102. In embodiments including theoptional heart stimulator 225, the control circuit 205 communicates withthe heart stimulator 225 via a communication signal 220. For example,the control circuit 205 may provide data concerning the cardiac activityof the heart to the heart stimulator 225 via the communication signal220.

The optional heart stimulator 225 generates stimulation pulses forstimulating the heart 102 (FIG. 3), and transmits the stimulation pulsesto the leads 104, 106, and 108 (FIG. 3) for stimulating the heart 102.The stimulation pulses may be capable of treating various heartconditions, such as arrhythmias, as is described more fully herein. Theheart stimulator 225 may generate the stimulation pulses based oncardiac activity received from the control circuit 205 via thecommunication signal 220.

FIG. 5 shows an exemplary, simplified block diagram depicting variouscomponents of the optional heart stimulator 215. The heart stimulator215 can be capable of treating both fast and slow arrhythmias withstimulation therapy, including cardioversion, defibrillation, and pacingstimulation. The heart stimulator 215 can be solely or further capableof delivering stimuli to autonomic nerves, non-myocardial tissue, othernerves, etc. While a particular multi-chamber device is shown, it is tobe appreciated and understood that this is done for illustrationpurposes only. Thus, the techniques and methods described below can beimplemented in connection with any suitably configured or configurablestimulation device. Accordingly, one of skill in the art could readilyduplicate, eliminate, or disable the appropriate circuitry in anydesired combination to provide a device capable of treating theappropriate chamber(s) or regions of a patient's heart withcardioversion, defibrillation, pacing stimulation, autonomic nervestimulation, non-myocardial tissue stimulation, other nerve stimulation,etc.

A housing 200 for the heart stimulator 215 is often referred to as the“can”, “case” or “case electrode”, and may be programmably selected toact as the return electrode for all “unipolar” modes. Housing 200 mayfurther be used as a return electrode alone or in combination with oneor more of the coil electrodes 126, 132 and 134 for shocking purposes.Housing 200 further includes a connector (not shown) having a pluralityof terminals 201, 202, 204, 206, 208, 212, 214, 216, 218, 221 (shownschematically and, for convenience, the names of the electrodes to whichthey are connected are shown next to the terminals).

To achieve right atrial sensing and/or pacing, the connector includes atleast a right atrial tip terminal (A_(R) TIP) 202 adapted for connectionto the atrial tip electrode 120. A right atrial ring terminal (A_(R)RING) 201 is also shown, which is adapted for connection to the atrialring electrode 121. To achieve left chamber sensing, pacing and/orshocking, the connector includes at least a left ventricular tipterminal (V_(L) TIP) 204, a left atrial ring terminal (A_(L) RING) 206,and a left atrial shocking terminal (A_(L) COIL) 208, which are adaptedfor connection to the left ventricular tip electrode 122, the leftatrial ring electrode 124, and the left atrial coil electrode 126,respectively. Connection to suitable autonomic nerve stimulationelectrodes or other tissue stimulation or sensing electrodes is alsopossible via these and/or other terminals such as a stimulation terminal(S ELEC) 221.

As discussed herein, where an electrode is suitable for stimulation,activation may also be provided using such an electrode. Activation mayalter a tissue, for example, to increase permeability of a nerve tothereby cause release of a neurochemical or to change properties of anerve to thereby decrease or increase its ability to transmit a signalor to release a neurochemical.

To support right chamber sensing, pacing, and/or shocking, the connectorfurther includes a right ventricular tip terminal (V_(R) TIP) 212, aright ventricular ring terminal (V_(R) RING) 214, a right ventricularshocking terminal (RV COIL) 216, and a superior vena cava shockingterminal (SVC COIL) 218, which are adapted for connection to the rightventricular tip electrode 128, right ventricular ring electrode 130, theRV coil electrode 132, and the SVC coil electrode 134, respectively.Connection to suitable autonomic nerve stimulation electrodes or othertissue stimulation or sensing electrodes is also possible via theseand/or other terminals such as the stimulation terminal 221.

At the core of the heart stimulator 215 is processor 220 that controlsthe various modes of stimulation therapy. The processor 220 may be aprogrammable microcontroller, a microprocessor, or an equivalent controlcircuitry, designed specifically for controlling the delivery ofstimulation therapy, and may further include RAM or ROM memory, logicand timing circuitry, state machine circuitry, and I/O circuitry.Typically, processor 220 includes the ability to process or monitorinput signals (data or information) as controlled by a program codestored in a designated block of memory. The type of microcontroller isnot critical to the described implementations. Rather, any suitableprocessor 220 may be used that carries out the functions describedherein. The use of microprocessor-based control circuits for performingtiming and data analysis functions are well known in the art.

Representative types of control circuitry that may be used in connectionwith the described embodiments can include the microprocessor-basedcontrol system of U.S. Pat. No. 4,940,052 (Mann et al.), thestate-machine of U.S. Pat. Nos. 4,712,555 (Sholder) and 4,944,298(Sholder), all of which are incorporated by reference herein. For a moredetailed description of the various timing intervals that may be usedwithin the heart stimulator 215 and their inter-relationship, see U.S.Pat. No. 4,788,980 (Mann et al.), also incorporated herein by reference.

FIG. 4 also shows an atrial pulse generator 222 and a ventricular pulsegenerator 224 that generate pacing stimulation pulses for delivery bythe right atrial lead 104, the coronary sinus lead 106, and/or the rightventricular lead 108 via an electrode configuration switch 226. It isunderstood that in order to provide stimulation therapy in each of thefour chambers of the heart the atrial and ventricular pulse generators,222 and 224, may include dedicated, independent pulse generators,multiplexed pulse generators, or shared pulse generators. The pulsegenerators 222 and 224 are controlled by the processor 220 viaappropriate control signals 228 and 230, respectively, to trigger orinhibit the stimulation pulses.

The processor 220 further includes timing control circuitry 232 tocontrol the timing of the stimulation pulses (e.g., pacing rate,atrio-ventricular (AV) delay, atrial interconduction (A-A) delay, orventricular interconduction (V-V) delay, etc.) as well as to keep trackof the timing of refractory periods, blanking intervals, noise detectionwindows, evoked response windows, alert intervals, marker channeltiming, etc., which is well known in the art.

The processor 220 further includes an arrhythmia detector 234, amorphology discrimination module 236, a capture detection module 237, alead portion module 238, an autonomic module 239 and optionally anorthostatic compensator and a minute ventilation (MV) response module,the latter two are not shown in FIG. 4. These components can be utilizedby the heart stimulator 215 for determining desirable times toadminister various therapies, including those to reduce the effects oforthostatic hypotension. The aforementioned components may beimplemented in hardware as part of the processor 220, or assoftware/firmware instructions programmed into the heart stimulator 215and executed on the processor 220 during certain modes of operation.

The lead portion module 238 may perform a variety of tasks related toelectrode polarity or electrode selection of an exemplary lead portion.For example, such a module may cause two electrodes to be electricallyconnected and have a polarity different than a third electrode of anexemplary lead portion. The lead portion module 238 optionally interactswith the autonomic module 239. The autonomic module 239 may determine orotherwise set timings and energy related parameters for activation of anautonomic nerve via an exemplary lead portion, as described furtherbelow.

The electronic configuration switch 226 includes a plurality of switchesfor connecting the desired electrodes to the appropriate I/O circuits,thereby providing complete electrode programmability. Accordingly,switch 226, in response to a control signal 242 from the processor 220,determines the polarity of the stimulation pulses (e.g., unipolar,bipolar, combipolar, etc.) by selectively closing the appropriatecombination of switches (not shown) as is known in the art.

An atrial sensing circuit 244 and a ventricular sensing circuit 246 mayalso be selectively coupled to the right atrial lead 104, coronary sinuslead 106, and the right ventricular lead 108, through the switch 226 fordetecting the presence of cardiac activity in each of the four chambersof the heart. Accordingly, the atrial (ATR. SENSE) and ventricular (VTR.SENSE) sensing circuits 244 and 246 may include dedicated senseamplifiers, multiplexed amplifiers, or shared amplifiers. Switch 226determines the “sensing polarity” of the cardiac signal by selectivelyclosing the appropriate switches, as is also known in the art. In thisway, the clinician may program the sensing polarity independent of thestimulation polarity. The sensing circuits 244 and 246 are optionallycapable of obtaining information indicative of tissue capture.

Each sensing circuit 244 and 246 preferably employs one or more lowpower, precision amplifiers with programmable gain and/or automatic gaincontrol, bandpass filtering, and a threshold detection circuit, as knownin the art, to selectively sense the cardiac signal of interest. Theautomatic gain control enables the heart stimulator 215 to dealeffectively with the difficult problem of sensing the low amplitudesignal characteristics of atrial or ventricular fibrillation.

The outputs of the atrial and ventricular sensing circuits 244 and 246are connected to the processor 220, which, in turn, is able to triggeror inhibit the atrial and ventricular pulse generators 222 and 224,respectively, in a demand fashion in response to the absence or presenceof cardiac activity in the appropriate chambers of the heart.Furthermore, as described herein, the processor 220 is also capable ofanalyzing information output from the sensing circuits 244 and 246and/or the data acquisition system 252 to determine or detect whethercapture has occurred and to program a pulse, or pulses, in response tosuch determinations. The sensing circuits 244 and 246, in turn, receivecontrol signals over signal lines 248 and 250 from the processor 220 forpurposes of controlling the gain, threshold, polarization charge removalcircuitry (not shown), and the timing of any blocking circuitry (notshown) coupled to the inputs of the sensing circuits 244 and 246.

For arrhythmia detection, the heart stimulator 215 utilizes the atrialand ventricular sensing circuits 244 and 246 to sense cardiac signals todetermine whether a rhythm is physiologic or pathologic. In reference toarrhythmias, as used herein, “sensing” is reserved for the noting of anelectrical signal or obtaining data (information), and “detection” isthe processing (analysis) of these sensed signals and noting thepresence of an arrhythmia. The timing intervals between sensed events(e.g., P-waves, R-waves, and depolarization signals associated withfibrillation which are sometimes referred to as “F-waves” or“Fib-waves”) are then classified by the arrhythmia detector 234 of theprocessor 220 by comparing them to a predefined rate zone limit (i.e.,bradycardia, normal, low rate VT, high rate VT, and fibrillation ratezones) and various other characteristics (e.g., sudden onset, stability,physiologic sensors, and morphology, etc.) in order to determine thetype of remedial therapy that is needed (e.g., bradycardia pacing,anti-tachycardia pacing, cardioversion shocks or defibrillation shocks,collectively referred to as “tiered therapy”).

The lead portion module 238 or the autonomic module 239 may operate inconjunction with the arrhythmia detector module 234. For example, thelead portion module 238 may select an electrode polarity for optimalactivation of a parasympathetic nerve and the autonomic module 239 maydetermine energy parameters such as frequency, pulse width, number ofpulses in a train, etc., for activation of the parasympathetic nerve. Inturn, activation of the parasympathetic nerve via an exemplary leadportion may produce a cardiac response that helps to detect or classifyan arrhythmia, for example, in coordination with the arrhythmia detectormodule 234.

Cardiac signals are also applied to inputs of an analog-to-digital (A/D)data acquisition system 252. The data acquisition system 252 isconfigured to acquire intracardiac electrogram signals, convert the rawanalog data into a digital signal, and store the digital signals forlater processing and/or telemetric transmission to an external device254. The data acquisition system 252 is coupled to the right atrial lead104, the coronary sinus lead 106, the right ventricular lead 108 and/orthe nerve or other tissue stimulation lead 110 through the switch 226 tosample cardiac signals across any pair of desired electrodes.

The processor 220 is further coupled to a memory 260 by a suitablecomputer bus 262 such as a data/address bus, wherein the programmableoperating parameters used by the processor 220 are stored and modified,as required, in order to customize the operation of the heart stimulator215 to suit the needs of a particular patient. Such operating parametersdefine, for example, pacing pulse amplitude, pulse duration, electrodepolarity, rate, sensitivity, automatic features, arrhythmia detectioncriteria, and the amplitude, wave shape, number of pulses, and vector ofeach shocking pulse to be delivered to the patient's heart 102 withineach respective tier of therapy. One feature of the describedembodiments is the ability to sense and store a relatively large amountof data (e.g., from the data acquisition system 252), which data maythen be used for subsequent analysis to guide the programming of theheart stimulator 215.

Advantageously, the operating parameters of the heart stimulator 215 maybe non-invasively programmed into the memory 260 through a telemetrycircuit 264 in telemetric communication via communication link 266 withthe external device 254, such as a programmer, transtelephonictransceiver, or a diagnostic system analyzer. The processor 220activates the telemetry circuit 264 with a control signal 268. Thetelemetry circuit 264 advantageously allows intracardiac electrogramsand status information relating to the operation of the heart stimulator215 (as contained in the processor 220 or memory 260) to be sent to theexternal device 254 through an established communication link 266.

The heart stimulator 215 can further include a physiologic sensor 270,commonly referred to as a “rate-responsive” sensor because it istypically used to adjust pacing stimulation rate according to theexercise state of the patient. The physiological sensor 270 may furtherbe used to detect changes in cardiac output (see, e.g., U.S. Pat. No.6,314,323, entitled “Heart stimulator determining cardiac output, bymeasuring the systolic pressure, for controlling the stimulation”, toEkwall, issued Nov. 6, 2001, which discusses a pressure sensor adaptedto sense pressure in a right ventricle and to generate an electricalpressure signal corresponding to the sensed pressure, an integratorsupplied with the pressure signal which integrates the pressure signalbetween a start time and a stop time to produce an integration resultthat corresponds to cardiac output), changes in the physiologicalcondition of the heart, or diurnal changes in activity (e.g., detectingsleep and wake states). Accordingly, the processor 220 responds byadjusting the various pacing parameters (such as rate, AV Delay, V-VDelay, etc.) at which the atrial and ventricular pulse generators, 222and 224, generate stimulation pulses.

With respect to physiological pressure sensors, commercially availablepressure transducers include those marketed by Millar Instruments(Houston, Tex.) under the mark MIKROTIP®. A study by Shioi et al.,“Rapamycin Attenuates Load-Induced Cardiac Hypertrophy in Mice”,Circulation 2003; 107:1664, measured left ventricular pressures in miceusing a Millar pressure transducer inserted through the LV apex andsecured in the LV apex with a purse-string suture using 5-0 silk.Various exemplary methods, devices, systems, etc., described hereinoptionally use such a pressure transducer to measure pressures in thebody (e.g., chamber of heart, vessel, etc.). Another company, RadiMedical Systems AB (Uppsala, Sweden), markets various lead-based sensorsfor intracoronary pressure measurements, coronary flow reservemeasurements and intravascular temperature measurements. Such sensortechnologies may be suitably adapted for use with an implantable devicefor in vivo measurements of physiology.

While shown as being included within the heart stimulator 215, it is tobe understood that the physiologic sensor 270 may also be external tothe heart stimulator 215, yet still be implanted within or carried bythe patient. Examples of physiologic sensors that may be implemented inthe heart stimulator 215 include known sensors that, for example, sensepressure, respiration rate, pH of blood, ventricular gradient, cardiacoutput, preload, afterload, contractility, and so forth. Another sensorthat may be used is one that detects activity variance, wherein anactivity sensor is monitored diurnally to detect the low variance in themeasurement corresponding to the sleep state. For a complete descriptionof the activity variance sensor, the reader is directed to U.S. Pat. No.5,476,483 (Bornzin et al.), issued Dec. 19, 1995, which patent is herebyincorporated by reference.

The companies Nellcor (Pleasanton, Calif.) and Masimo Corporation(Irvine, Calif.) market pulse oximeters that may be used externally(e.g., finger, toe, etc.). Where desired, information from such externalsensors may be communicated wirelessly to the heart stimulator 215, forexample, via an implantable device programmer. Other sensors may beimplantable and suitably connected to or in communication with the heartstimulator 215. Technology exists for lead-based oximeters. For example,a study by Tsukada et al., “Development of catheter-type optical oxygensensor and applications to bioinstrumentation,” Biosens Bioelectron,2003 Oct. 15; 18(12):1439-45, reported use of a catheter-type opticaloxygen sensor based on phosphorescence lifetime.

The physiological sensors 270 optionally include sensors for detectingmovement and minute ventilation in the patient. The physiologicalsensors 270 may include a position sensor and/or a minute ventilation(MV) sensor to sense minute ventilation, which is defined as the totalvolume of air that moves in and out of a patient's lungs in a minute.Signals generated by the position sensor and MV sensor are passed to theprocessor 220 for analysis in determining whether to adjust the pacingrate, etc. The processor 220 monitors the signals for indications of thepatient's position and activity status, such as whether the patient isclimbing upstairs or descending downstairs or whether the patient issitting up after lying down.

The heart stimulator 215 optionally includes circuitry capable ofsensing heart sounds and/or vibration associated with events thatproduce heart sounds. Such circuitry may include an accelerometer asconventionally used for patient position and/or activity determinations.Accelerometers typically include two or three sensors aligned alongorthogonal axes. For example, a commercially availablemicro-electromechanical system (MEMS) marketed as the ADXL202 by AnalogDevices, Inc. (Norwood, Mass.) has a mass of about 5 grams and a 14 leadCERPAK (approx. 10 mm by 10 mm by 5 mm or a volume of approx. 500 mm³).The ADXL202 MEMS is a dual-axis accelerometer on a single monolithicintegrated circuit and includes polysilicon springs that provide aresistance against acceleration forces. The term MEMS has been definedgenerally as a system or device having micro-circuitry on a tiny siliconchip into which some mechanical device such as a mirror or a sensor hasbeen manufactured. The aforementioned ADXL202 MEMS includesmicro-circuitry and a mechanical oscillator.

The heart stimulator 215 additionally includes an energy source 276 suchas a battery that provides operating power to all of the circuits shownin FIG. 4. For the heart stimulator 215, which employs shocking therapy,the energy source 276 is capable of operating at low current drains forlong periods of time (e.g., preferably less than 10 μA), and is capableof providing high-current pulses (for capacitor charging) when thepatient requires a shock pulse (e.g., preferably, in excess of 2 A, atvoltages above 200 V, for periods of 10 seconds or more). The energysource 276 also desirably has a predictable discharge characteristic sothat elective replacement time can be detected.

The heart stimulator 215 can further include magnet detection circuitry(not shown), coupled to the processor 220, to detect when a magnet isplaced over the heart stimulator 215. A magnet may be used by aclinician to perform various test functions of the heart stimulator 215and/or to signal the processor 220 that the external programmer 254 isin place to receive or transmit data to the processor 220 through thetelemetry circuits 264. Trigger IEGM storage also can be achieved bymagnet.

The heart stimulator 215 further includes an impedance measuring circuit278 that is enabled by the processor 220 via a control signal 280. Theknown uses for an impedance measuring circuit 278 include, but are notlimited to, lead impedance surveillance during the acute and chronicphases for proper lead positioning or dislodgement; detecting operableelectrodes and automatically switching to an operable pair ifdislodgement occurs; measuring respiration or minute ventilation;measuring thoracic impedance for determining shock thresholds (e.g.,heart failure indications such as pulmonary edema and other factors);detecting when the heart stimulator 215 has been implanted; measuringstroke volume; and detecting the opening of heart valves, etc. Theimpedance measuring circuit 278 is advantageously coupled to the switch226 so that any desired electrode may be used. The impedance measuringcircuit 278 optionally provides information to the lead portion module238 or the autonomic module 239.

In the case where the heart stimulator 215 is intended to operate as animplantable cardioverter/defibrillator (ICD) device, it detects theoccurrence of an arrhythmia, and automatically applies an appropriatetherapy to the heart aimed at terminating the detected arrhythmia. Tothis end, the processor 220 further controls a shocking circuit 282 byway of a control signal 284. The shocking circuit 282 generates shockingpulses in a range of joules, for example, conventionally up to about 40J, as controlled by the processor 220. Such shocking pulses are appliedto the patient's heart 102 through at least two shocking electrodes, andas shown in this embodiment, selected from the left atrial coilelectrode 126, the RV coil electrode 132, and/or the SVC coil electrode134. As noted above, the housing 200 may act as an active electrode incombination with the RV electrode 132, or as part of a split electricalvector using the SVC coil electrode 134 or the left atrial coilelectrode 126 (i.e., using the RV electrode as a common electrode).

Cardioversion level shocks are generally considered to be of low tomoderate energy level (so as to minimize pain felt by the patient),and/or synchronized with an R-wave and/or pertaining to the treatment oftachycardia. Defibrillation shocks are generally of moderate to highenergy level (i.e., corresponding to thresholds in the range ofapproximately 5 J to approximately 40 J), delivered asynchronously(since R-waves may be too disorganized), and pertaining exclusively tothe treatment of fibrillation. Accordingly, the processor 220 is capableof controlling the synchronous or asynchronous delivery of the shockingpulses.

In low-energy cardioversion, an ICD device typically delivers acardioversion stimulus (e.g., 0.1 J, etc.) synchronously with a QRScomplex; thus, avoiding the vulnerable period of the T wave and avoidingan increased risk of initiation of VF. In general, if antitachycardiapacing or cardioversion fails to terminate a tachycardia, then, forexample, after a programmed time interval or if the tachycardiaaccelerates, the ICD device initiates defibrillation therapy.

While an ICD device may reserve defibrillation as a latter tier therapy,it may use defibrillation as a first-tier therapy for VF. In general, anICD device does not synchronize defibrillation therapy with any givenportion of a ECG. Again, defibrillation therapy typically involveshigh-energy shocks (e.g., 5 J to 40 J), which can include monophasic orunidirectional and/or biphasic or bidirectional shock waveforms.Defibrillation may also include delivery of pulses over two currentpathways.

Various exemplary methods, devices, systems, etc., described hereinpertain to activation of tissue. Various exemplary electrode-bearinglead portions are suitable for placement in a venous structure (e.g.,SVC, CS, etc.). Such exemplary lead portions may have a pre-shapedconfiguration or an adjustable configuration. Such exemplary leadportions include one or more electrodes. In general, such exemplary leadportions include one or more extensions where one extension includes aconnector suitable for electrically connecting the lead portion to animplantable device.

FIG. 6 shows an exemplary electrode-bearing lead portion 410 suitablefor positioning in a venous structure such as a vagal nerve. Theexemplary lead portion 410 includes a helical configuration. A helix,sometimes also called a coil, is a curve for which the tangent makes aconstant angle with a fixed line. The shortest path between two pointson a cylinder (one not directly above the other) is a fractional turn ofa helix (e.g., consider the paths taken by squirrels chasing one anotherup and around tree trunks). Helices come in enantiomorphous left- (coilscounterclockwise as it “goes away”) and right-handed forms (coilsclockwise).

A helix is a space curve with parametric equations: x=r* cos (t); y=r*sin (t); and z=c*t, for t within a range of 0 to 27π, where r is theradius of the helix and c is a constant giving the vertical separationof the helix's loops. Other equations exist to describe arc length,torsion, etc. Other possible configurations include, for example,conical spirals, Poinsot's spirals, polygonal spirals, sphericalspirals, semi-spherical spirals, slinky (e.g., spiral wound around ahelix), etc.

The lead portion 410 includes a helical configuration that includesthree electrodes 412, 414, 416. Such a lead portion may include one ormore electrodes. Such electrodes may be controlled by the heartstimulator 215 to act as anodes or cathodes. In general, theconfiguration acts to help secure the lead portion 410 at a particularlocation, for example, in a vein.

FIG. 7 shows an exemplary electrode-bearing lead portion 510 suitablefor positioning in a venous structure such as a vagal nerve. Theexemplary lead portion 510 includes a helical configuration. The leadportion 510 includes a helical configuration that includes threeelectrodes 522, 524, 526 and a distal extension 528. The helical portionmay include one or more electrodes and the distal extension 528 mayinclude additional electrodes. Such electrodes may be controlled by theheart stimulator 215 to act as anodes or cathodes. The helicalconfiguration may act to help secure the lead portion 510 at aparticular location, for example, in a vein. One or more additionalfeatures associated with the distal extension 528 may act to help securethe lead portion 520 at a particular location.

FIG. 8 shows an exemplary electrode-bearing lead portion 610 suitablefor positioning in a venous structure such as a vagal nerve. Theexemplary lead portion 610 includes a helical configuration. The leadportion 610 includes a securing loop 631 and a helical configurationthat includes three electrodes 632, 634, 636. Such a lead portion mayinclude one or more electrodes. Such electrodes may be controlled by theheart stimulator 215 to act as anodes or cathodes. In general, thesecuring loop 631 acts to help secure the lead portion 610 at aparticular location, for example, in a vein.

FIG. 9 shows an exemplary electrode-bearing lead portion 710 suitablefor positioning in a venous structure such as a vagal nerve. Theexemplary lead portion 710 includes a helical configuration. The leadportion 710 includes a securing loop 741, a helical configuration thatincludes three electrodes 742, 744, 746 and a distal extension 748. Thehelical portion may include one or more electrodes and the distalextension 748 may include additional electrodes. Such electrodes may becontrolled by the heart stimulator 215 to act as anodes or cathodes. Ingeneral, the securing loop 741 acts to help secure the lead portion 740at a particular location, for example, in a vein. One or more additionalfeatures associated with the distal extension 748 may act to help securethe lead portion 740 at a particular location.

As described herein such exemplary electrode-bearing lead portions 410,510, 610 or 710 may be positioned in a venous structure (e.g., lumen ofthe structure) and used to activation nerves or tissue. FIG. 10 belowshows various nerve pathways with respect to venous structures. Inparticular, the nerve pathways may have various orientations withrespect to the course of a venous structure. Further, depending on theorientation relationship between a nerve and venous structure, selectiveor optimal activation of the nerve may be achieved using an exemplaryelectrode-bearing lead portion 410, 510, 610 or 710.

FIG. 10 shows an approximate anatomical diagram 800 that includes theheart 102 and various other structures. In particular, the diagram 800illustrates the right branch of a vagal nerve 880. The vagal nerve isalso known as the vagus nerve or tenth cranial nerve. The vagal nerve880 is part of the autonomic system and regarded primarily as aparasympathetic nerve. Various autonomic nerve bundles and plexusesexist that include a mixture of parasympathetic and sympathetic nerves.

An article by Kawashima, “The autonomic nervous system of the humanheart with special reference to its origin, course, and peripheraldistribution”, Anat Embryol (2005) 209: 425-438 discloses various nervepathways including parasympathetic cardiac branches arising from vagusnerve. The Kawashima article classified vagal cardiac branches withdirect connections or connections via the cardiac plexus, excludingbranches of the lung or surrounding vessels and organs, as follows:superior cardiac branch 881, which arose from the vagus nerve at aboutthe level of the upper (proximal) portion of the recurrent laryngealnerve branch 882; inferior cardiac branch 883, which arose from therecurrent laryngeal nerve branch 882; and thoracic cardiac branch 884,which arose from the vagus nerve at about the level of the lower(distal) portion of the recurrent laryngeal nerve branch 882.

The diagram 800 shows approximate locations of these branches 881, 883,884, with respect to the superior vena cava (SVC) 860, the innominateartery 866 (also known as the brachiocephalic trunk), and the trachea864. The dashed lines indicate that the right vagal nerve 880 and itsvarious branches are not in the fore of the diagram 800 but rather liegenerally aft of the SVC 860. Further the dashed lines do not indicateany particular length but rather a general course of such branches asthey extend to, or around, the heart and other structures. The diagram800 illustrates approximate orientation relationships between the venousstructures such as the SVC 860 and the right vagal nerve 880 and itsvarious branches. In particular, the orientation relationship betweenthe SVC 860 and the right vagal nerve 880 varies as does the orientationrelationship between the SVC 860 and the various branches of the vagalnerve 880.

Kawashima reported that the superior cardiac branch 881 was observed onthe right side and the left side (e.g., for the left vagus, not shown),with one to five branches observed in each individual; that the inferiorcardiac branch 883 was also observed on the right side and the leftside, with one to four branches (average of 2.1 branches; 2.4 rightbranches, 1.9 left branches); and that the thoracic cardiac branch 884was observed more so on the right side (18 subjects) compared to theleft side (10 subjects), with one to five branches (average of 2.0branches; 2.6 right branches, 1.4 left branches).

Kawashima reported that the right cardiac plexus usually surrounded thebrachiocephalic trunk 866 (which branches into the right subclavian andright carotid arteries), whereas the left cardiac plexus surrounded theaortic arch. Furthermore, the cardiac plexus surrounding the greatvessels on both sides was made from a larger cardiac plexus between theaortic arch and the pulmonary arterial trunk through the ventral/dorsalaspect of the aortic arch. On the right side, several nerves wereobserved passing through the dorsal, rather than the ventral, aspect ofthe aortic arch. On the left side, no differences between the ventraland dorsal courses to the aortic arch were observed.

Various nerves identified in the Kawashima article extend to one or moreepicardial autonomic plexuses. For example, Pauza et al., “Morphology,distribution, and variability of the epicardiac neural ganglionatedsubplexuses in the human heart”, The Anatomical Record 259(4): 353-382(2000), reported that the epicardial plexus includes seven subplexuses:(I) left coronary, (II) right coronary, (III) ventral right atrial, (IV)ventral left atrial, (V) left dorsal, (VI) middle dorsal, and (VII)dorsal right atrial. The Pauza article states that, in general, thehuman right atrium is innervated by two subplexuses (III, VII), the leftatrium by three subplexuses (IV, V, VI), the right ventricle by onesubplexus (II), and the left ventricle by three subplexuses (I, V, VI).The Pauza article also notes that diagrams from Mizeres, “The cardiacplexus in man”, Am. J. Anat. 112:141-151 (1963), suggest that “leftepicardiac subplexuses may be considered as being formed by nervesderived from the left side of the deep extrinsic cardiac plexus, whereasventral and dorsal right atrial subplexuses should be considered asbeing supplied by preganglionated nerves extending from the right vagusnerve and right sympathetic trunk, as their branches course in theadventitia of the right pulmonary artery and superior vena cava”. ThePauza article also states that the left coronary (I), right coronary(II), ventral left atrial (IV) and middle dorsal (VI) subplexuses “maybe considered as being formed by the deep extrinsic plexus that receivesequally from both vagi and sympathetic trunks”,

With respect to activation of autonomic nerves, end terminals (orterminal knobs) of the postganglionic sympathetic nerves (e.g.,epicardial postganglionic sympathetic nerves) release norepinephrine,which can act upon the myocardium. Heart rate, although initiallystimulated by norepinephrine, usually decreases over time due toactivation of baroreceptors and vagal-mediated (parasympathetic) slowingof the heart rate.

Upon activation, a vagus nerve releases the hormone acetylcholine at itsvagal endings and is, therefore, cholinergic. This is in contrast withadrenergic systems which cause the release of epinephrine andnorepinephrine. In general, the release of acetylcholine, rather thanthe passing of nerve impulses, initiates a specific response at an organ(e.g., the heart, etc.), recognizing that parasympathetic input to thebrain is typically associated with a more complex mechanism, which mayoccur depending on stimulation site or stimulation parameters.

Regarding the cardiac branches, parasympathetic vagi nerves aredistributed to regions of the sinoatrial (SA) node and theatrioventricular (AV) node where parasympathetic cholinergic muscarinicreceptors can act on the SA node to decrease heart rate and act on theAV node to decrease conduction velocity. Release of acetylcholine tothese regions typically results in both a decrease in the rate of rhythmof the SA node, as well as a decrease in the cardiac impulsetransmission into the ventricles. Consequences of these actionsgenerally include a decrease in heart rate, cardiac output, ventricularcontraction, arterial blood pressure, as well as a decrease in overallventricular pumping.

Electrical stimulation of autonomic nerves has been reported in theliterature, see, e.g., Murakami et al., “Effects of cardiac sympatheticnerve stimulation on the left ventricular end-systolic pressure-volumerelationship and plasma norepinephrine dynamics in dogs”, Jpn. Circ. J.61(10): 864-71 (1997); and Du et al., “Response to cardiac sympatheticactivation in transgenic mice overexpressing beta 2-adrenergicreceptor”. Am-J-Physiol. Aug; 271(2 Pt 2): H630-6 (1996). Magneticstimulation of nerves has also been reported, for example, where a nerveis exposed to a time-varying magnetic field, which may induce electricalcurrents in the nerve.

According to various exemplary technologies described herein, a pulse, aseries of pulses, or a pulse train, can be delivered via an exemplaryelectrode-bearing lead portion, for example, operably connected to heartstimulator 215 to thereby activate an autonomic nerve, other nerve ortissue. The exemplary electrode-bearing lead portion may be used toselectively activate a nerve or optimally activate a nerve through itsconfiguration and optionally through selection of and polarity of one ormore electrodes.

A pulse or pulse train optionally includes pulse parameters or pulsetrain parameters, such as, but not limited to, frequency, pulse duration(or pulse width), number of pulses or amplitude. These parameters mayhave broad ranges and vary over time within any given pulse train. Ingeneral, a power level for individual pulses or pulse trains isdetermined based on these parameters or other parameters.

Exemplary ranges for pulse frequency for nerve or tissue stimulationinclude frequencies ranging from approximately 0.1 to approximately 100Hz, and, in particular, frequencies ranging from approximately 1 Hz toapproximately 20 Hz. Of course, higher frequencies higher than 100 Hzmay also be suitable. Exemplary ranges for pulse duration, or pulsewidth for an individual pulse (generally within a pulse train), includepulse widths ranging from approximately 0.01 milliseconds toapproximately 5 milliseconds and, in particular, pulse widths rangingfrom approximately 0.1 milliseconds to approximately 2 milliseconds.Exemplary pulse amplitudes are typically given in terms of current orvoltage; however, a pulse or a pulse trains may also be specified bypower, charge and/or energy. For example, in terms of current, exemplaryranges for pulse amplitude include amplitudes ranging from approximately0.02 mA to approximately 20 mA, in particular, ranging from 0.1 mA toapproximately 5 mA. Exemplary ranges for pulse amplitude in terms ofvoltage include voltages ranging from approximately 2 V to approximately50 V, in particular, ranging from approximately 1 V to approximately 20V.

FIG. 11 shows an exemplary lead 902 positioned in the SVC 860. In thisexample, the vagal nerve 880 has a right branch 885 that extends at anoblique angle to the lumen of the SVC 860. The lead 902 includes anexemplary lead portion 910 positioned to stimulate the right vagalbranch 885. For example, the rotation from the proximal to the distalend of the helix is clockwise so as to position the lead portion 910primarily along the dorsal wall of the SVC 860 closer to the branch 885and descending in approximately the same angle as the branch 885. Incontrast, a counterclockwise rotation would cause the descending helixto have an angle more orthogonal to the branch 885, as coursing alongthe dorsal wall of the SVC 860. Thus, given that branches of the rightvagal nerve generally descend and are proximate the dorsal or left wallof the SVC, then a clockwise rotation may be preferred should one chooseto align the lead portion with such a branch or branches. Should onechoose to have an orthogonal orientation proximate to such a branch orbranches, then a counterclockwise rotation may be used.

As explained with respect to the examples of FIGS. 4-7, theconfiguration of the exemplary lead portion 910 contributes to thisability to selectively or optimally activation the desired nerve. One ormore other variables may aid in selective or optimal activation of thedesired nerve (e.g., stimulation parameters). Further, activation mayaim to have a positive or negative effect (e.g., to inhibit or to inducecertain action).

The lead 902 includes a mechanism for aid in positioning the leadportion 910 that optionally includes a stylet or pull wire. Theexemplary lead 902 is optionally stylet-driven and optionally siliconeinsulated. The exemplary lead 902 includes one or more electrodes 904 or906, such as, titanium nitride (TiN) coated platinum-iridium electrodes.Suitable electrodes may be ring, plate (e.g., outwardly directed), or ofother shape.

The lead portion 910 is optionally a pre-shaped helix that allows forpassive fixation. For example, when a stylet is inserted into the leadportion 910, the lead portion 910 straightens to enhancemaneuverability. Complete withdrawal of the stylet from the lead portion910 allows the pre-shaped helix to press against the walls of the veinand provide some degree of positional stability. Various components ofthe exemplary arrangement 900 are optionally part of a catheter deliverysystem for an exemplary lead portion.

While pre-shaping is possible, the lead portion 910 may be optionallyshaped in situ through use of a mechanism such as a wire or sheathinserted into the lead portion 910 such that it acquires a helicalshape.

A catheter delivery system may include a kink resistant, lubricioussheath, which maintains high radial strength, yet softens in vivo forflexible performance. Peel away features may be used as well as a valveadapter, which can be removed or attached as required, to provide forhemostasis on demand, while reducing air aspiration and back bleeding.An optional sidearm attachment can allow for line flushing and contrastinjection. An optional inflatable balloon can create venous backpressure and allow a care provider to block venous flow, for example, toallow for injection of contrast media for visualization of any structurethat may aid in the positioning of an exemplary lead portion.

FIG. 12 shows an exemplary lead portion 1010 including one or moreelectrodes 1012, 1014, 1016. The exemplary lead portion 1010 may bepre-shaped or shaped in situ, either by any of a variety of techniques.

FIG. 13 shows an exemplary lead portion 1110 including one or moreelectrodes 1112, 1114, 1116. In the exemplary lead portion 1110, theadjacent electrodes 1112, 1114, and 1116 are positioned at an angle ofabout 34 degrees.

FIG. 14 shows an exemplary lead portion 1210 including one or moreelectrodes 1212, 1214, 1216. In the exemplary lead portion 1210, theadjacent electrodes 1212, 1214, and 1216 are positioned at an angle ofabout 22 degrees.

FIG. 15 shows an exemplary lead portion 1310 including one or moreelectrodes 1312, 1314, 1316. In the exemplary lead portion 1310, theadjacent electrodes 1312, 1314, 1316 are positioned at an angle of aboutzero degrees (e.g., perpendicular to the proximal end (upper end) of thelead portion 1313.

FIG. 16 shows as end view of an exemplary lead portion 1410 includingone or more electrodes 1412, 1414, 1416. In the exemplary lead portion1410, the rotational direction of the helix may be clockwise (CW) orcounterclockwise (CCW). Referring again to the example of FIG. 9, therotation from proximal to distal end of the helix is clockwise so as toposition the lead portion 1410 primarily along the dorsal wall of theSVC 860 closer to the branch 885 and substantially parallel to thebranch 885. The exemplary lead portion 1410 also shows an exemplarypolarity pattern for the three electrodes 1412, 1414, 1416 where theelectrode 1414 (e.g., the middle electrode) has a polarity differentthan that of the electrodes 1412, 1416. Other examples may use otherpolarities or different number of electrodes.

FIG. 17 shows a flowchart for an exemplary method 1500 of treating anischemia of the heart 102 (FIG. 3). In step 1505, electrical pulses aregenerated below a cardiac threshold (i.e., subcardiac thresholdelectrical pulses) of the heart 102 (FIG. 3). The energy of theelectrical pulses is such that the beat rate of the heart 102 is notreduced. In one embodiment, the vagal nerve stimulator 215 (FIG. 4)generates the electrical pulses and the control circuit 205 (FIG. 4)controls the energy of the electrical pulses. The control circuit 205may control the frequency, duration, voltage amplitude, currentamplitude, pulse width, pulse shape, and timing of the electricalpulses, as is described more fully herein.

In step 1510, the electrical pulses are transmitted to a vagal nerve 880(FIG. 10) for treating an ischemia of the heart 102 (FIG. 3). In oneembodiment, the lead 110 (FIGS. 3 and 4) transmits the electrical pulsesto one or more electrodes 144, 144′, or 144″ (FIG. 3) located inproximity of the vagal nerve 880. The electrodes 144, 144′, or 144″ mayinclude a lead portion such as lead portion 410 (FIG. 6), lead portion510 (FIG. 7), lead portion 610 (FIG. 8), lead portion 710 (FIG. 9), leadportion 1210 (FIG. 14), lead portion 1310 (FIG. 15), or lead portion1410 (FIG. 16). Alternatively, the electrode 144, 144′, or 144″ mayinclude the lead 902 (FIG. 11).

FIG. 18 shows a flowchart for an exemplary method 1600 of treating anischemia of the heart 102 (FIG. 3). In step 1605, cardiac activity ofthe heart 102 (FIG. 3) is sensed. The sensed cardiac activity mayinclude R-waves or R-waves occurring in the heart 102. In oneembodiment, the vagal nerve stimulator 215 (FIG. 4) senses the cardiacactivity by receiving electrical signals, which are indicative of thecardiac activity, from one or more of the electrodes 144, 144′, or 144″(FIG. 3) via the lead 110 (FIGS. 3 and 4). In a further embodiment, thevagal nerve stimulator 215 also receives these electrical signals viathe case 200, which acts as an electrode.

In step 1610, an ischemia of the heart 102 (FIG. 3) is detected based onthe sensed cardiac activity. In one embodiment, the control circuit 205(FIG. 2) detects the ischemia based on the sensed cardiac activity. Forexample, the control circuit 205 may be a microprocessor ormicrocontroller programmed to detect the ischemia based on the sensedcardiac activity. One commonly used method to detect ischemic episodesfrom the heart's electrical activity is to monitor the repolarization.Using the IEGM sensed from electrodes on leads that are positionedeither on the device can, subcutaneously, epicardially, endocardially,the ST segment is detected and monitored for any deviation or elevationfrom it normal baseline level. Another approach is described in U.S.patent application Ser. No. 11/061008 filed on Feb. 17, 2005, entitled“Systems and Methods for Detecting Ischemic Events”, herein incorporatedby reference.

In step 1615, electrical pulses are generated below a cardiac threshold(i.e., subcardiac threshold electrical pulses) of the heart 102 (FIG.3). The energy of the electrical pulses is such that the beat rate ofthe heart 102 is not reduced. In one embodiment, the vagal nervestimulator 215 (FIG. 4) generates the electrical pulses and the controlcircuit 205 (FIG. 4) controls the energy of the electrical pulses. Thecontrol circuit 205 may control the frequency, duration, voltageamplitude, current amplitude, pulse width, pulse shape, and timing ofthe electrical pulses, as is described more fully herein.

In one embodiment, the control circuit 205 controls the energy of theelectrical pulses based on the cardiac activity. The control circuit 205may increase the energy of the electrical pulses until the sensedcardiac activity indicates a reduction of the beat rate of the heart102. The control circuit 205 can then reduce the energy of theelectrical pulses to restore the previous heart beat rate. In this way,the control circuit 205 can maximize the energy of the electrical pulsessuch that the beat rate of the heart 102 is not reduced by theelectrical pulses.

In step 1620, the electrical pulses are transmitted to a vagal nerve 880(FIG. 10) for treating an ischemia of the heart 102 (FIG. 3). In oneembodiment, the lead 110 (FIG. 3) transmits the electrical pulses to oneor more electrodes 144, 144′, or 144″ (FIG. 3) located in proximity ofthe vagal nerve 880. The electrodes 144, 144′, or 144″ may include alead portion such as lead portion 410 (FIG. 6), lead portion 510 (FIG.7), lead portion 610 (FIG. 8), lead portion 710 (FIG. 9), lead portion1210 (FIG. 14), lead portion 1310 (FIG. 15), or lead portion 1410 (FIG.16). Alternatively, the electrode 144, 144′, or 144″ may include thelead 902 (FIG. 11).

FIG. 19 shows a flowchart for an exemplary method 1700 of lowering adefibrillation threshold of the heart 102 (FIG. 3). In step 1705,electrical pulses are generated below a cardiac threshold (i.e.,subcardiac threshold electrical pulses) of the heart 102 (FIG. 3). Theenergy of the electrical pulses is such that the beat rate of the heart102 is not reduced. In one embodiment, the vagal nerve stimulator 215(FIG. 4) generates the electrical pulses and the control circuit 205(FIG. 4) controls the energy of the electrical pulses. The controlcircuit 205 may control the frequency, duration, voltage amplitude,current amplitude, pulse width, pulse shape, and timing of theelectrical pulses, as is described more fully herein.

In step 1710, the electrical pulses are transmitted to a vagal nerve 880(FIG. 10) for reducing a defibrillation threshold of the heart 102 (FIG.3). In one embodiment, the lead 110 (FIGS. 3 and 4) transmits theelectrical pulses to one or more electrodes 144, 144′, or 144″ (FIG. 3)located in proximity of the vagal nerve 880. The electrodes 144, 144′,or 144″ may include a lead portion such as lead portion 410 (FIG. 6),lead portion 510

(FIG. 7), lead portion 610 (FIG. 8), lead portion 710 (FIG. 9), leadportion 1210 (FIG. 14), lead portion 1310 (FIG. 15), or lead portion1410 (FIG. 16). Alternatively, the electrode 144, 144′, or 144″ mayinclude the lead 902 (FIG. 11).

Although exemplary methods, devices, systems, etc., have been describedin language specific to structural features and/or methodological acts,it is to be understood that the subject matter defined in the appendedclaims is not necessarily limited to the specific features or actsdescribed. Rather, the specific features and acts are disclosed asexemplary forms of implementing the claimed methods, devices, systems,etc.

1. An implantable stimulation apparatus comprising: a) a vagal nervestimulator configured to generate electrical pulses having an energyinsufficient to slow a patient's heart rate; b) a first electrodecoupled to the vagal nerve stimulator and configured to transmit theelectrical pulses to a vagal nerve so as to at least one of: (1) inhibitinjury resulting from an ischemia; or (2) reduce injury resulting froman ischemia; c) a second electrode configured to sense cardiac activityof a patient's heart; and d) a control circuit coupled to the secondelectrode and the vagal nerve stimulator, wherein the control circuit:uses the cardiac activity to determine an energy of the electricalpulses at which the patient's heart rate is not slowed; and adjustsenergy parameters of the electrical pulses so that the energy of theelectric pulses is insufficient to slow the patient's heart rate.
 2. Theimplantable stimulation apparatus of claim 1, wherein the controlcircuit further detects the ischemia.
 3. The implantable stimulationapparatus of claim 1, wherein the control circuit further detects aheart arrhythmia based on the cardiac activity, the implantablestimulation device further comprising: a) a third electrode configuredto transmit stimulation pulses to the heart; and b) a heart stimulatorcoupled to the third electrode and configured to generate thestimulation pulses for treating the heart arrhythmia.
 4. The implantablestimulation apparatus of claim 1, wherein the first electrode comprisesat least one of: (a) a flexible flap for wrapping around the vagalnerve; or (b) a helix shape for wrapping around the vagal nerve.
 5. Theimplantable stimulation apparatus of claim 1, wherein the vagal nervestimulator is configured to supply electrical pulses comprising: (a) afrequency in a range of about 10 Hertz to about 100 Hertz; (b) a pulsewidth in a range of about 100 microseconds to about 5 milliseconds; (c)a voltage amplitude in a range of 0.5 volts to 20 volts; and (d) acurrent below 20 milliamps.
 6. The implantable stimulation apparatus ofclaim 5, wherein the vagal nerve stimulator is configured to supplyelectrical pulses comprising a current below 1 milliamp.
 7. Theimplantable stimulation apparatus of claim 1, wherein the vagal nervestimulator is configured so as to be capable of supplying electricalpulses comprising at least one of: (a) continuous pulses; (b) periodicpulses; or (c) event triggered pulses.
 8. An implantable stimulationapparatus comprising: a) a first electrode configured to sense cardiacactivity of a heart; b) a vagal nerve stimulator configured to generateelectrical pulses having an energy sufficient to treat ischemia withoutslowing of the heart rate; c) a second electrode coupled to the vagalnerve stimulator and configured to transmit the electrical pulses to avagal nerve for treating an ischemia; and d) a controller coupled to thefirst electrode and the vagal nerve stimulator, wherein the controller:controls the vagal nerve stimulator based on the cardiac activity, andreduces the energy of the electrical pulses if the sensed cardiacactivity indicates a reduction of the beat rate of the heart.
 9. Theimplantable stimulation apparatus of claim 8, wherein the controllerfurther detects the ischemia based on the cardiac activity.
 10. Theimplantable stimulation apparatus of claim 8, wherein the controllerfurther detects a heart arrhythmia based on the cardiac activity, theimplantable stimulation device further comprising: a) a third electrodeconfigured to transmit stimulation pulses to the heart; and b) a heartstimulator coupled to the third electrode and configured to generate thestimulation pulses for treating the heart arrhythmia.
 11. Theimplantable stimulation apparatus of claim 8, wherein the vagal nervestimulator is configured so as to be capable of supplying electricalpulses comprising at least one of: (a) continuous pulses; (b) periodicpulses; or (c) event triggered pulses.
 12. A method comprising:determining an energy of electrical pulses sufficient to treat ischemiain a patient without slowing of the patient's heart rate when deliveredto a vagal nerve; generating electrical pulses having said energysufficient to treat ischemia in a patient without slowing of thepatient's heart rate; and treating an ischemia by transmitting theelectrical pulses to the vagal nerve.
 13. The method of claim 12,wherein treating the ischemia comprises transmitting the electricalpulses to the vagal nerve to reduce injury resulting from the ischemia.14. The method of claim 12, wherein treating the ischemia comprisestransmitting the electrical pulses to the vagal nerve to inhibit injuryresulting from the ischemia.
 15. The method of claim 12, furthercomprising: sensing cardiac activity of the heart, wherein the energy ofthe electrical pulses is determined based on the cardiac activity. 16.The method of claim 12, wherein the electrical pulses have: (a) afrequency in a range of 10 Hertz to 100 Hertz (b) a pulse width in arange of 100 microseconds to 5 milliseconds; (c) a voltage amplitude ina range of 0.5 volts to 20 volts; and (d) a current below 20 milliamps.17. The method of claim 6, wherein the electrical pulses have a currentbelow 1 milliamp.
 18. The method of claim 12, wherein the electricalpulses are periodic electrical pulses.
 19. A method comprising: sensingcardiac activity of a heart; detecting an ischemia based on the cardiacactivity; determining an energy of electrical pulses effective to treatischemia in a patient when delivered to a vagal nerve without slowing ofthe patient's heart rate based on the cardiac activity of the patient;generating electrical pulses having an energy sufficient to treatischemia in a patient without slowing of the patient's heart rate; andtransmitting the electrical pulses having said energy sufficient totreat ischemia in a patient without slowing of the patient's heart rateto the vagal nerve for treating an ischemia.
 20. The method of claim 19,further comprising controlling the energy of the electrical pulses basedon the cardiac activity.